Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice
Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01832/full |
| _version_ | 1811265501681156096 |
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| author | Stephanie M. Matt Stephanie M. Matt Jacob M. Allen Marcus A. Lawson Lucy J. Mailing Jeffrey A. Woods Jeffrey A. Woods Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson |
| author_facet | Stephanie M. Matt Stephanie M. Matt Jacob M. Allen Marcus A. Lawson Lucy J. Mailing Jeffrey A. Woods Jeffrey A. Woods Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson |
| author_sort | Stephanie M. Matt |
| collection | DOAJ |
| description | Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits. |
| first_indexed | 2024-04-12T20:24:56Z |
| format | Article |
| id | doaj.art-4ee0809fabf34ea4a394b0d2a219fd35 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T20:24:56Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4ee0809fabf34ea4a394b0d2a219fd352022-12-22T03:17:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01832386847Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in MiceStephanie M. Matt0Stephanie M. Matt1Jacob M. Allen2Marcus A. Lawson3Lucy J. Mailing4Jeffrey A. Woods5Jeffrey A. Woods6Rodney W. Johnson7Rodney W. Johnson8Rodney W. Johnson9Rodney W. Johnson10Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDivision of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDivision of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesNeuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDivision of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesIntegrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesAging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.https://www.frontiersin.org/article/10.3389/fimmu.2018.01832/fullmicrogliabutyrateagingneuroinflammationepigeneticsmicrobiome |
| spellingShingle | Stephanie M. Matt Stephanie M. Matt Jacob M. Allen Marcus A. Lawson Lucy J. Mailing Jeffrey A. Woods Jeffrey A. Woods Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson Rodney W. Johnson Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice Frontiers in Immunology microglia butyrate aging neuroinflammation epigenetics microbiome |
| title | Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice |
| title_full | Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice |
| title_fullStr | Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice |
| title_full_unstemmed | Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice |
| title_short | Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice |
| title_sort | butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice |
| topic | microglia butyrate aging neuroinflammation epigenetics microbiome |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01832/full |
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